Elsevier

Gynecologic Oncology

Volume 112, Issue 2, February 2009, Pages 314-318
Gynecologic Oncology

Expression and amplification of eIF-5A2 in human epithelial ovarian tumors and overexpression of EIF-5A2 is a new independent predictor of outcome in patients with ovarian carcinoma

https://doi.org/10.1016/j.ygyno.2008.10.024Get rights and content

Abstract

Objectives

Our previous study has suggested an oncogenic role of eIF-5A2 in ovarian tumorigenesis. Abnormalities of eIF-5A2 and its clinical/prognostic significance, however, in ovarian carcinoma are unclear.

Methods

In this study, we examined expression of EIF-5A2, using immunohistochemistry, in 30 normal ovaries, 30 ovarian cystadenomas, 30 borderline ovarian tumors and 110 ovarian carcinomas. The amplification status of eIF-5A2 in each ovarian carcinoma was assessed by fluorescence in situ hybridization.

Results

Overexpression of EIF-5A2 was detected in none of the normal ovaries, 7% cystadenomas, 30% borderline tumors, and 53% invasive ovarian carcinomas, respectively. Amplification of eIF-5A2 was detected in 16% of informative ovarian carcinomas. In ovarian carcinomas, significant positive associations were found between overexpression of EIF-5A2 and the tumors ascending grade, later pT/pN and FIGO stages, as well as increased positive rate of Ki-67 (p < 0.05). In univariate survival analysis of the ovarian carcinoma cohorts, a significant association of overexpression of EIF-5A2 with shortened patient survival (mean 39.0 months vs 69.5 months, p < 0.001) was demonstrated. Importantly, EIF-5A2 expression provided significant independent prognostic parameters in multivariate analysis (p = 0.043).

Conclusions

These findings suggest that increased expression of EIF-5A2 in ovarian carcinoma may represent an acquired malignant phenotypic feature of tumor cells, and the overexpression of EIF-5A2, as detected by immunohistochemistry, is an independent molecular marker for shortened survival time of patients with ovarian carcinoma.

Introduction

Ovarian cancer is a major cause of death among all gynecological malignancies. It is the seventh most common cancer in women worldwide and is the fourth leading cause of death from cancer among American women [1]. Recently, its incidence has been increasing in Asian countries such as China and Singapore [2]. Because of its insidious onset, 70% of ovarian cancer patients were diagnosed at advanced stage, and the prognosis is very poor with a 5-year survival rate of < 20% [3]. Ovarian carcinoma is the most common histopathological type of ovarian cancer. The development of ovarian carcinoma is considered as a multi-step process involving multiple genetic changes [4]. Recurrent chromosomal changes in ovarian carcinoma have been extensively analyzed by comparative genomic hybridization (CGH) with several amplified regions including 3q or parts of 3q, being reported [5], [6], [7], [8]. Amplification of 3q also has been detected frequently in other solid malignant tumors including esophageal carcinoma [9], lung carcinoma [10], gastric carcinoma [11], colorectal carcinoma [12] and other neoplasms [13], [14], suggesting that human chromosome 3q contains oncogenes related to tumorigenesis and progression of a number of different solid tumors.

Using a chromosome microdissection-hybrid selection method, we have previously isolated a novel candidate oncogene, eIF-5A2 (eukaryotic initiation factor 5A2), from a primary ovarian cancer cell line UACC-1598 containing a high-copy-number amplification of 3q26 [15]. Recently, tumorigenic characteristics of eIF-5A2 have been demonstrated by both in vitro and in vivo assays [16]. Up-regulated expression of eIF-5A2 was observed in gastric and colorectal carcinomas and it was associated with a higher risk of tumor metastasis [17], [18], [19]. These findings suggest that eIF-5A2 might function as a putative oncogene in the tumorigenesis of several types of human cancers. In this study, the expression dynamics of EIF-5A2 in a series of human ovarian tissue, normal and pathological, non-neoplastic and neoplastic, were examined. The clinicopathological and prognostic significance of overexpression of EIF-5A2 in our ovarian carcinoma cohorts was also assessed.

Section snippets

Patients and tissue specimens

A total of 170 epithelial ovarian tumors (benign, borderline and carcinomatous) and 30 normal ovaries were obtained from archives of paraffin-embedded tissues between 1990 and 2001 at the Department of Pathology, Cancer Center and the First affiliated Hospital, Sun Yat-Sen University, Guangzhou, China. The cancer cases selected were based on availability of resection tissue and follow-up data. The ovarian tumor cases encompassed 110 histologically confirmed invasive carcinomas, 30 borderline

EIF-5A2 expression in ovarian tissues

For EIF-5A2 IHC staining in ovarian tissues, because the expression of EIF-5A2 in the surface epithelium of all 30 normal ovarian surface epithelium was negative (0) or weak (1) (Fig. 1A), the staining index in the normal ovaries was determined to be less or equal to 3. Therefore, we designated the staining index of 0–3 as the normal expression of EIF-5A2 (Figs. 1A and B), while staining index of 4–12 was depicted as overexpression of this protein (Figs. 1C and E). Using this designation, the

Discussion

Recently, we have isolated a novel candidate oncogene, eIF-5A2, from a primary ovarian cancer cell line UACC-1598 containing a high-copy-number amplification of 3q26 [15]. To investigate whether or not up-regulated expression of EIF-5A2 is involved in the pathogenesis of ovarian carcinoma, in the present report, the expression of EIF-5A2 was examined firstly by IHC in normal ovaries, benign and borderline epithelial ovarian tumors, and malignant epithelial cancers. Our results demonstrate that

Conflict of interest statement

The authors declare that there are no conflicts of interest.

Acknowledgments

This study was supported in part by the Major State Basic Research Program of China (2006CB910104), the Nature Science Foundation of China (No.30772334 and 30772475), Key Special Project of Guangdong Science and technology Agency (2005A30801001) and Hong Kong Research Grant Council Grant (HKU7656/07M).

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